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Lecture 4

NURSING 2LA2 Lecture Notes - Lecture 4: Phenelzine, Neuroendocrinology, Reboxetine

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Ruth Hannon

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Module 4: Depression
Mood disorders are disorders of emotion, including mania and depression. 10% of
Canadians are affected. These disorders are highly underdiagnosed and undertreated. Depression
is among the leading cause of disability worldwide, with approximately 8% of adults
experiencing major depressive episodes at some time in their lives. Suicide is estimated to be the
cause of death in up to 15% of individuals with major depressive disorder. The prevalence of
major depression among women is double that in men. It is thought that the reason for this is that
women are more apt to recognize mental health issues and go to their doctor.
In research conducted by the National Institute for Mental Health, they found that when
speaking to men in focus groups, depression often becomes masked. For example, in sematic
complaints, like migraines, back pain, or irritable bowel syndrome, it is therefore often not
recognized as depression. The true neurological basis for the increased prevalence in women is
unknown, but is also thought to be related to differences in hormonal status, or stress response
systems, or to sexual differences between the sexes in any of several brain areas. The prevalence
of bipolar disorder or manic depression is approximately 1% in the population at large,
approximately equally distributed between men and women.
Learning Outcomes
Objectives for today are:
1. To gain a basic understanding of the pathophysiology ofdepression
2. To describe the risk factors and symptoms of depression
3. To understand the process of neurotransmission
4. To identify which neurotransmitters are implicated indepression and how they work
5. To explain the anatomical changes associated withdepression
6. To describe the neuroendocrine system changes associatedwith depression
7. To identify treatments for depression includingpharmacological and non-pharmacological
therapies anddescribe how
DSM-IV-TR Criteria for Depression
Mood disorders are disorders of emotion including mania and depression. For this module, we
will be focusing on Depressive Disorders which are commonly divided into two categories:
Major Depressive Disorder which is characterized by a persistent unpleasant mood
Dysthymia which is characterized by chronic mild depressive symptoms (so the
symptoms are the same, they’re just in a milder form in dysthymia)
The DSM 4 Diagnostic Criteria for a Major Depressive Disorder include the simultaneous
presence of 5 or more of the following symptoms during a 2 week period. These represent a
change from previous functioning.
Major Depressive Disorder
Depressed mood
Anhedonia (inability to experience pleasure)
Feelings of worthlessness or excessive guilt

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Decreased concentration
Psychomotor agitation or retardation, insomnia or hypersomnia, decreased libido
Change in weight or appetite
Thoughts of death or suicide ideation
Sub Classifications of Depression
I will not be focusing on these sub classifications. Several medical illnesses such as diabetes,
heart disease, autoimmune disorders and pain are common comorbid diagnoses.
Melancholic features, atypical depression
Depression with psychotic features
Depression with catatonic features
Postpartum specifier
Risk Factors for Depression
The following is a list of risk factors or environmental in-life history events that can contribute to
the etiology of depression.
Childhood emotional, physical, and sexual abuses
Prior episode of depression
Family history of depressive disorder
Lack of social support
Stressful life event
Current substance abuse
Economic difficulties
Etiology of Depression
The etiology of depression is:
Dynamic interplay amongst:
oGenetic predisposition
oLife history
oBiological challenges
Much of the research in the past 40 years has focused on the deficits in the neurotransmitter
systems. It is currently believed that major depressive disorders arise from the complex
interactions of genes and environmental factors.

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Brain Math
Pathophysiology is the study of what happens at the cellular level to cause disease. For
the pathophysiology of mental illness, we are talking about what happens inside the brain. That
portion of the central nervous system is contained within the cranium. So let’s do a little bit of
brain math. There are about 100 billion neurons or nerve cells, and 10-50 trillion neuroglia which
support the nerve cells in the brain. The brain has a mass of about 1300 grams or 3 pounds in
adults. On average, each neuron performs 1000 synapses with other neurons. The total numbers
of synapses is about 1000 trillion, which is larger than the number of stars in the galaxy. Just
from these numbers, you can conclude that the brain is a very complex organ and it is quite
complex to try and understand how it works and what happens at the cellular level, or in this
case, the level of the neuron to cause depression.
Genetic-Environment Interaction
So now, let’s talk about the genetic component of depression. Major depression is more
common amongst first degree relatives than the general population. Family, twin, and adoption
studies suggest the hereditary component to the etiology of mood disorders. Hereditability for
depression has been estimated from twin studies as 31-42% with a substantial contribution of
environmental effects unique to individuals of 58-67%. So again, the cause is partly genetics and
partly environment.
Scientist have not identified a gene or a series of genes that cause depression, rather
certain variations in genes, called polymorphisms may increase the risk for depression. Genes
can predispose individuals to major depressive disorder in many ways. For example, genes help
control the metabolism of neurotransmitters and their receptors, the number of particular types of
neurons and their synaptic connections, the intracellular transduction of neuronal signals, and the
speed with which all of these can change in response to environmental stressors.
The serotonin transporter gene is the most studied in major depressive disorder. This
gene is of interest because it contains a polymorphism that gives rise to two different alleles, long
and short. As you know, people usually have two copies of each gene in their DNA. Therefore, a
person can be homozygous for the long allele, homozygous for the short allele, or heterozygous,
one long and one short. The short allele slows down the synthesis of the serotonin transporter.
This is thought to reduce the speed with which serotonin neurons can adapt to changes in their
Serotonin is one of the neurotransmitters implicated in depression and we will talk about
this in more detail a little later on. At present, it just important to remember that the short allele
in a serotonin transporter gene slows down the synthesis of the serotonin transporter, leading to
the dysregulation of serotonin, and that this process has been implicated for depression.
Genetic Predisposition: Brain Derived Nerotropic Factor (BDNF)
BDNF is also implicated in depression. BDNF is a growth factor that:
Plays an Important role in birth, survival and maturation of brain cells during
oAs described in the article, BDNF is a protein found in high concentrations in the
brain. BDNF is important for neuronal cell growth and well as the synaptic
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